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From: Állan Ferrari <ajrferrari.gmail.com>

Date: Sat, 22 Aug 2020 17:59:45 -0300

Dear Amber user community,

I am interested in simulating a protein - small molecule inhibitor

interaction.

I optimized the small molecule geometry with Gaussian and derived RESP

charges.

Also, with parmchk2 I derived frcmod files containing small molecule

parameters to prepare the system for simulation using both parm10 and gaff.

However, there are still some missing parameters or parameters with high

penalty score totalizing 12 parameters among one bond, couple angles and

dihedrals.

I have tried for days to use paramfit following this tutorial (

http://ambermd.org/tutorials/advanced/tutorial23/ ) but with no success.

In my first attempt, I have tried to generate a large number of conformers

(> 1000) with random values for the angles and dihedrals I am interested in

parametrizing. Then, I runned Gaussian to evaluate its energy (constrained,

single point energy calculation). When I tried to derive K (the

difference between Amber energy and quantum energy, in Hartree) using

paramfit the fit was horrible (R2 was negative!).

In a second attempt, I tried to generate only the r_eq and bond force

constant for one bond. I generaeed 50 conformers with random distances

between the two atoms of interest (0.5 to 3.5 A), runned gaussian single

energy point calculation for each and when it came to derive K again an

horrible fit (r2 < 0.05)! I tried to continue the tutorial regardless of

the poor fit but it didn't work, as expected. It complained I had

insufficient bond information in sample structures. Definitely not the case.

Finally, I was hoping that I could derive manually the parameters, once I

have the energies as a function of the distance between the atoms.

I fit k*(r-r0) function to the derived (E, r) data points. The k, however,

is equal to 4.5 while the k for bonds already found from parm10 and gaff

files are in the 200-600 value range.

Questions:

1) Is this last attempt a valid approach, that is, vary the degree of

freedom I am interested in parametrize and then manually fit to obtain the

missing parameters?

2) Is there a multiplying factor for this parameter (10E-2?) that would

justify the difference I am observing (4.5 to 200-600)?

If (1) is not an option, I would really appreciate a better

tutorial/documentation for paramfit or other source for small molecule

amber parametrization...

Kind regards,

Állan

_______________________________________________

AMBER mailing list

AMBER.ambermd.org

http://lists.ambermd.org/mailman/listinfo/amber

Received on Sat Aug 22 2020 - 14:30:03 PDT

Date: Sat, 22 Aug 2020 17:59:45 -0300

Dear Amber user community,

I am interested in simulating a protein - small molecule inhibitor

interaction.

I optimized the small molecule geometry with Gaussian and derived RESP

charges.

Also, with parmchk2 I derived frcmod files containing small molecule

parameters to prepare the system for simulation using both parm10 and gaff.

However, there are still some missing parameters or parameters with high

penalty score totalizing 12 parameters among one bond, couple angles and

dihedrals.

I have tried for days to use paramfit following this tutorial (

http://ambermd.org/tutorials/advanced/tutorial23/ ) but with no success.

In my first attempt, I have tried to generate a large number of conformers

(> 1000) with random values for the angles and dihedrals I am interested in

parametrizing. Then, I runned Gaussian to evaluate its energy (constrained,

single point energy calculation). When I tried to derive K (the

difference between Amber energy and quantum energy, in Hartree) using

paramfit the fit was horrible (R2 was negative!).

In a second attempt, I tried to generate only the r_eq and bond force

constant for one bond. I generaeed 50 conformers with random distances

between the two atoms of interest (0.5 to 3.5 A), runned gaussian single

energy point calculation for each and when it came to derive K again an

horrible fit (r2 < 0.05)! I tried to continue the tutorial regardless of

the poor fit but it didn't work, as expected. It complained I had

insufficient bond information in sample structures. Definitely not the case.

Finally, I was hoping that I could derive manually the parameters, once I

have the energies as a function of the distance between the atoms.

I fit k*(r-r0) function to the derived (E, r) data points. The k, however,

is equal to 4.5 while the k for bonds already found from parm10 and gaff

files are in the 200-600 value range.

Questions:

1) Is this last attempt a valid approach, that is, vary the degree of

freedom I am interested in parametrize and then manually fit to obtain the

missing parameters?

2) Is there a multiplying factor for this parameter (10E-2?) that would

justify the difference I am observing (4.5 to 200-600)?

If (1) is not an option, I would really appreciate a better

tutorial/documentation for paramfit or other source for small molecule

amber parametrization...

Kind regards,

Állan

_______________________________________________

AMBER mailing list

AMBER.ambermd.org

http://lists.ambermd.org/mailman/listinfo/amber

Received on Sat Aug 22 2020 - 14:30:03 PDT

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